Dataset Information

Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis.

ABSTRACT: Identifying new mechanisms that underlie the complex process of metastasis is vital to combat this fatal step in prostate cancer (PCa) progression. Small non-coding RNAs are emerging as important regulators of tumor cell biology. Here we take an integrative approach to elucidate the contribution of microRNAs to metastatic progression, combining transcriptomic analysis with functional screens for migration and morphology. We developed high-content microscopy, high-throughput functional screens for migration and morphology in PCa cells using a microRNA library. RNA-Seq analysis of paired epithelial and mesenchymal PCa cells identified differential expression of 200 microRNAs. Data integration identified two microRNAs that inhibited migration, induced an epithelial-like morphology and were increased in epithelial PCa cells. An overrepresentation of the AAGUGC seed sequence was detected in all three datasets. Analysis of published datasets of patients with PCa identified microRNAs of clinical relevance. The integration of high-throughput functional and expression analyses identifies microRNAs with clinical significance that modulate metastatic behavior in PCa.

SUBMITTER: Rao SR

PROVIDER: S-EPMC7082744 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis.

Rao Srinivasa R SR Howarth Alison A Kratschmer Patrick P Snaith Ann E AE Yapp Clarence C Ebner Daniel D Hamdy Freddie C FC Edwards Claire M CM

Frontiers in oncology 20200313

Identifying new mechanisms that underlie the complex process of metastasis is vital to combat this fatal step in prostate cancer (PCa) progression. Small non-coding RNAs are emerging as important regulators of tumor cell biology. Here we take an integrative approach to elucidate the contribution of microRNAs to metastatic progression, combining transcriptomic analysis with functional screens for migration and morphology. We developed high-content microscopy, high-throughput functional screens fo ...[more]

PMID: 32231998

Similar Datasets

Project description:Prostate Cancer (PCa) overdiagnosis and overtreatment, as a consequence of the limited specificity of current detection and prognostication methods, remains a major challenge in clinical practice. Therefore, development and validation of new molecular biomarkers amenable of detecting clinically significant disease is crucial. MicroRNAs (miRNA) deregulation is common in cancer, constituting potential non-invasive biomarkers for PCa detection and prognostication. Herein, we evaluated the screening and prognostic biomarker potential of two onco-microRNAs (miR-182-5p and miR-375-3p) in liquid biopsies (plasma) of PCa patients with clinically localized disease undergoing curative-intent treatment. A first cohort of 98 PCa and 15 normal prostates were used to assess PCa-specificity of miR-182-5p in tissues. A cohort composed of PCa 252 patients and 52 asymptomatic controls allowed for assessment of diagnostic and prognostic value in plasmas. After RNA extraction from tissue and plasma samples, cDNA synthesis specific for miRNAs was performed followed by measurement of miR-182-5p and miR-375-3p relative expression by RT-qPCR, using U6 snRNA gene as reference. MiR-182-5p was significantly overexpressed in PCa tissues (p < 0.0001) and in plasma of PCa patients (p = 0.0020), compared to respective controls. Moreover, miR-182-5p expression identified PCa with AUC = 0.81 (95% CI: 0.725-0.892, p = 0.0001) in tissue and with 77% specificity and 99% NPV (AUC = 0.64, 95% CI: 0.561-0.709, p = 0.0021) in plasma. Both circulating miR-182-5p and miR-375-3p levels associated with more advanced pathologic stage and the former was significantly higher in patients that developed metastasis (p = 0.0145). Indeed, at the time of diagnosis, circulating miR-375-3p levels predicted which patients would develop metastasis, with almost 50% sensitivity, 76% specificity, and a NPV of 89% (AUC = 0.62, 95% CI: 0.529-0.713, p = 0.0149). We conclude that these two circulating miRNAs might be clinical useful as non-invasive biomarkers for detection and prediction of metastasis development at the diagnosis together with clinical variables used in routine practice.

Dataset Information

Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis.

Publications

Transcriptomic and Functional Screens Reveal MicroRNAs That Modulate Prostate Cancer Metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets